Abstract
The clinical significance of bone defects is not well understood; these pathological conditions not only compromise patients' quality of life but may also result in permanent functional impairment if inadequately addressed. Consequently, the development of effective therapeutic interventions for bone defect repair and regeneration is a critical medical challenge. Recent advancements in nanotechnology, particularly engineered nanoparticle systems, have introduced promising new strategies for bone tissue regeneration. However, it is important to note that most nanoparticle-based approaches remain at the preclinical or experimental stage, and their clinical translation is still limited. These sophisticated nanomaterials enhance critical biological processes including osteoconduction, osteoinduction, and osteogenesis which collectively facilitate optimal bone healing. Notably, certain nanoparticles possess intrinsic properties that enable modulation of the inflammatory microenvironment and immunological responses during bone repair. Furthermore, the integration of nanoparticles with complementary biomaterials yielded composite systems with superior therapeutic efficacy in addressing complex bone defects. This comprehensive review summarizes the pathophysiological mechanisms underlying bone repair, systematically examines the preclinical and experimental therapeutic applications of various nanoparticle formulations across different phases of the bone-healing cascade, highlights recent technological innovations in nanoparticle engineering for enhanced bone regeneration, and critically discusses the existing limitations and challenges of clinical translation as well as promising future research directions in this rapidly evolving field.